The principal objectives of this research are to ascertain the role of the discrete nature of the oxygen carrying component of blood (particulate red cells suspended in plasma) on intracapillary and pericapillary oxygen exchange. Fundamental understanding of these processes has been based on the assumptions that capillary blood is a continuum hemoglobin solution and that the oxygen transport resistance within systemic capillaries is negligible relative to that in the tissue. Recent evidence argues against both assumptions. This research will permit a better understanding of oxygen exchange at the capillary level, both pulmonary uptake and systemic release, and will provide new insight for unravelling the mechanisms of oxygen rgulation in living tissues. A quantitative description of intracapillary oxygen transport will be developed that directly addresses the two-phase nature of capillary blood. Such a description is difficult with existing in-vivo experimental techniques and thus a model will be used to bridge the gap between intracapillary oxygen transport and experimentally measurable quantities. Oxygen uptake and release from single red cells and from red cells flowing in single-file suspension through capillary-size channels will be studied. These studies will determine intra-erthrocyte and intracapillary oxygen conductances. Results will be compared against in-vitro experimental data of oxygen uptake and release from single red cells and from red cells flowing in suspension through microchannels. The roles of red cell shape, size, spacing, and spacing heterogeneity in capillaries will be ascertained, as will be the functional capillary surface area for oxygen exchange. The intracapillary descriptio and results will be combined with models for the extravascular transport of oxygen. These studies will ascertain the extent to which tissue transport processes, with and without myoglobin, smooth-out the discrete oxygen supply from capillaries. The focus will be primarily on the role of the spacing and spacing heterogeneity of red cells in capillaries. The resistance to oxygen transport within capillaries will be compared to that in surrounding tissue by examining the drop in oxygen tension from red cells to tissue. The predicted result will be compared to available experimental data.